Dissecting the pathological effects of human Abeta40 and Abeta42 in Drosophila: a potential model for Alzheimer's disease

Iijima, K., Liu, H. P., Chiang, A. S., Hearn, S. A., Konsolaki, M., Zhong, Y. (April 2004) Dissecting the pathological effects of human Abeta40 and Abeta42 in Drosophila: a potential model for Alzheimer's disease. Proc Natl Acad Sci U S A, 101 (17). pp. 6623-8. ISSN 0027-8424 (Print)

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URL: https://www.ncbi.nlm.nih.gov/pubmed/15069204
DOI: 10.1073/pnas.0400895101


Accumulation of amyloid-beta (Abeta) peptides in the brain has been suggested to be the primary event in sequential progression of Alzheimer's disease (AD). Here, we use Drosophila to examine whether expression of either the human Abeta40 or Abeta42 peptide in the Drosophila brain can induce pathological phenotypes resembling AD. The expression of Abeta42 led to the formation of diffused amyloid deposits, age-dependent learning defects, and extensive neurodegeneration. In contrast, expression of Abeta40 caused only age-dependent learning defects but did not lead to the formation of amyloid deposits or neurodegeneration. These results strongly suggest that accumulation of Abeta42 in the brain is sufficient to cause behavioral deficits and neurodegeneration. Moreover, Drosophila may serve as a model for facilitating the understanding of molecular mechanisms underlying Abeta toxicity and the discovery of novel therapeutic targets for AD.

Item Type: Paper
Uncontrolled Keywords: Aging pathology Alzheimer Disease genetics metabolism pathology physiopathology Amyloid beta-Protein genetics metabolism physiology Animals Animals Genetically Modified genetics Behavior Animal Brain metabolism pathology Disease Models Animal Drosophila genetics Humans Mass Spectrometry Peptide Fragments genetics metabolism physiology
Subjects: diseases & disorders > mental disorders > delirium dementia cognitive disorders > Alzheimer's disease
organism description > animal > insect > Drosophila
CSHL Authors:
Communities: CSHL labs > Zhong lab
Depositing User: CSHL Librarian
Date: 27 April 2004
Date Deposited: 03 Feb 2012 15:22
Last Modified: 09 Nov 2017 17:10
PMCID: PMC404095
Related URLs:
URI: https://repository.cshl.edu/id/eprint/22395

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